Tobacco smoking is causally associated with cancer of the lung, upper aerodigestive tract, pancreas, kidney, and urinary bladder and is associated with cancer of the liver, uterine cervix and with leukemia. Involuntary smoking gives rise to some risk of cancer. Tobacco chewing, especially snuff dipping, is causally associated with cancer of the oral cavity and pharynx. Tobacco smoke and its particulate matter are carcinogenic in mice, rats and hamsters. Snuff is tumorigenic in the oral cavity of rats. It is the overall goal of the Program Project to contribute to an understanding of the carcinogenicity of tobacco smoke and of smokeless tobacco and to elucidate the mechanisms involved in the development of tumors induced by tobacco carcinogenesis. Five projects are proposed. 1. Study of the activation of tobacco-specific nitrosamines (TSNA) in humans and human risk assessment by measuring adducts of the carcinogenic TSNA, PAH and aromatic amines with DNA and with globin. 2. Analysis of tobacco for nitrosamino acids, cigarette smoke analysis for aromatic and heterocyclic amines and for nitrohydrocarbons, environmental tobacco smoke analysis for 3-venylpyridine. Cervical mucus will be examined for alkaloids and TSNA. 7. Study of the carcinogenesis of smokeless tobacco and betel quid. 10. Study of the mechanisms of the carcinogenic effects of tobacco smoke carcinogenic effects of tobacco smoke carcinogens in the oral cavity and esophagus of humans. 5. Development of biomarkers in smokers for the uptake of benzene.